He was a member of the Kappa Sigma Fraternity - Tau Chapter and graduated in 1941 from the University of Texas, then went on to complete his medical degree and his surgical training at Johns Hopkins. Following his graduation he went to London to work with Lord Russell Brock.
He performed the first successful human heart transplant in the United States in 1968. In 1969, he became the first heart surgeon to implant an artificial heart designed by Dr Domingo Liotta in a man.
Cooley and his associates have performed more than 100,000 open heart operations--more than any other group in the world. Denton Cooley has been in a band of doctors called "The Heartbeats." He played the string bass. In highschool, he played basketball. When he was younger, he discovered that he very much enjoyed golf. He has been golfing for 66 years. In the HBO film Something the Lord Made, Dr. Cooley was portrayed by Timothy J. Scanlin, Jr.
Cooley reportedly answered in the affirmative when a lawyer during a trial asked him if he considered himself to be the best heart surgeon in the world. “Don’t you think that’s being rather immodest?” the lawyer replied. “Perhaps,” Dr. Cooley responded. “But remember I’m under oath.”
Cooley filed for bankruptcy in 1988 citing real estate debts during a market downturn.
During the 2000 U.S. Presidential Elections Dr. Cooley was asked by then candidate George W. Bush to review VP candidate Dick Cheney's medical records, particularly concerning the status of his chronic heart condition.
Dr. Denton Cooley and the legendary heart surgeon, Dr. Michael E. DeBakey had a professional rivalry that lasted more than 50 years. They recently made amends in a public rapprochement on November 7, 2007 when DeBakey was 99 years old and Cooley was 87.
In addition, Cooley has authored or co-authored more than 1,300 scientific articles and 13 books.